Molecular Dynamics and Mechanical Behavior of Collagen Type I and its Lysine/Hydroxylysine-derived Crosslinks
| dc.contributor.author | Kwansa, Albert Lawrence | en |
| dc.contributor.committeechair | Freeman, Joseph W. | en |
| dc.contributor.committeechair | De Vita, Raffaella | en |
| dc.contributor.committeemember | Bevan, David R. | en |
| dc.contributor.committeemember | Gabler, Hampton Clay | en |
| dc.contributor.committeemember | Etzkorn, Felicia A. | en |
| dc.contributor.department | Biomedical Engineering | en |
| dc.date.accessioned | 2014-11-26T07:01:03Z | en |
| dc.date.available | 2014-11-26T07:01:03Z | en |
| dc.date.issued | 2013-06-03 | en |
| dc.description.abstract | Collagen type I is an extracellular matrix (ECM) protein that affords tensile strength and biological scaffolding to numerous vertebrate and invertebrate tissues. This strength has been attributed to the triple-helical structure of the collagen type I molecules, their organization into fibrils, and the presence of inter-molecular, covalent, enzymatic crosslinks. There are several different types of these crosslinks; their composition is tissue-specific and dependent upon factors such as age and health. Furthermore, these enzymatic crosslinks tend to form specifically at amino/N- and carboxy/C-terminal crosslinking sites. The mechanical behavior of collagen type I has been investigated, via experiment and theory, at the level of the molecule, microfibril, fibril, and fiber. However, the influence of different enzymatic crosslinks and their location (e.g., N- vs. C-site) on the mechanics of collagen type I has not been investigated in the literature. We employed molecular dynamics to model the mechanical behavior of uncrosslinked and crosslinked ~23-nm-long molecular segments and ~65-nm-long microfibril units of collagen type I. We then used these molecular simulations to construct a model of a single collagen type I fibril by considering the ~65-nm-long microfibril units arranged in series and then in parallel. When a uniaxial deformation was applied along the long axis of the molecular models, N-crosslinks aligned rapidly at lower strains followed by C-crosslinks more gradually at higher strains, leading to a two-stage crosslink recruitment. Then when comparing the influence of different enzymatic crosslinks, significant differences were observed for the high-strain elastic moduli of our microfibril unit models, namely and in increasing order, uncrosslinked, immature crosslinked (HLKNL and deH-HLNL), mature HHL-crosslinked, and mature PYD-crosslinked. At the fibril level, our low- and high-strain elastic moduli were in good agreement with some literature data, but in over-estimation of several other literature reports. Future work will seek to address simplifications and limitations in our modeling approach. A model such as this, accounting for different enzymatic crosslink types, may allow for the prediction of the mechanics of collagen fibrils and collagenous tissues, in representation of healthy and diseased states. | en |
| dc.description.degree | Ph. D. | en |
| dc.format.medium | ETD | en |
| dc.identifier.other | vt_gsexam:720 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/50933 | en |
| dc.publisher | Virginia Tech | en |
| dc.rights | In Copyright | en |
| dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | en |
| dc.subject | Fibril-forming | en |
| dc.subject | Fibrillar | en |
| dc.subject | Cross-link | en |
| dc.subject | Strain Energy | en |
| dc.subject | Elastic Modulus | en |
| dc.title | Molecular Dynamics and Mechanical Behavior of Collagen Type I and its Lysine/Hydroxylysine-derived Crosslinks | en |
| dc.type | Dissertation | en |
| thesis.degree.discipline | Biomedical Engineering | en |
| thesis.degree.grantor | Virginia Polytechnic Institute and State University | en |
| thesis.degree.level | doctoral | en |
| thesis.degree.name | Ph. D. | en |